This invention relates to a device and methods for renal nerve modulation, and more particularly, to ablation of the renal nerve using thermal energy.
Radiofrequency (RF) based thermal energy has been shown to effectively ablate nerves, and therefore prevent neurological impulses from crossing the ablated region. For patients with high blood pressure (BP), or hypertension (HTN), RF neuromodulation has been demonstrated to lower their BP (See, e.g., References 1-9 herein). Reducing a patient's BP may be particularly important if they have resistant HTN, whereby even multiple medications are insufficient to produce controlled systolic and diastolic pressures below 140 and 90 mm Hg, respectively.
RF neuromodulation, however, has potential negative side effects. Because RF devices achieve ablation via delivering heat, the device destroys nerve function by burning or cooking the axons running with the renal artery. Though this produces the desired effect on the nerve, the heat produced by the RF device causes pain and must be delivered from the tip of the catheter, requiring multiple ablations in different segments of the artery to avoid circumferential impact upon the renal artery wall and/or its lining RF ablation has been shown to cause scarring, strictures and clotting, or thrombosis, in other vessels.
Most notably, RF ablations surrounding the pulmonary vein within the right atrium of the heart to eliminate cardiac arrhythmias has caused strictures of the pulmonary vein with severe consequences. Therefore, to avoid renal artery strictures, or stenoses, circumferential RF ablation inside the renal artery to cause neural modulation is currently avoided by performing RF ablation in quadrants, along different segments of the renal artery. However, it is unknown whether the untreated quadrants may give rise to future greater relapse rates of HTN due to regrowth of the renal nerve in the non-ablated quadrants.
In addition, adjacent tissues in the kidneys, the collecting system for urine, have been subject to problematic scarring and strictures when RF ablation has been used to treat cancerous kidney tumors.
There is thus a need for a less painful method to treat a circumferential, or near-circumferential, segment of one or more renal arteries without the known risks associated with the RF ablation as described above.
Various patents describe renal neuromodulation by use of cold temperatures below 0° C. to produce some nerve dysfunction, at least for a transient period. See U.S. Pat. Nos. 7,617,005; 7,717,948; and 7,853,333. However, these patents describe only one embodiment that used Peltier thermoelectric cooling to produce nerve dysfunction. While thermoelectric cooling may be feasible within a catheter, it is unlikely to produce the sufficient low temperatures needed for durable renal nerve ablation.
Cryoablation, or freezing of tissue to lethal temperatures, has been used for tissue ablation in many locations within the body, mainly for tumors. Current cryotechnology using the Joule-Thompson effect, or JT cooling, produced by rapidly expanding gases, can achieve target temperatures within tissue of −40° C. However, the actual cooling capacity, or power, is quite limited due to the inefficiencies of cooling with a cryogen in a predominant gaseous state (e.g., thermal conductivity of gases is much less than liquids). This severely limits the propagation of sufficient lethal temperatures into tissues surrounding a cryoprobe, even when the surface of a JT cryoprobe using argon can be as low as −150° C. at the surface.
The above mentioned shortcoming in current JT cryoprobes becomes particularly evident in high heat sink scenarios, such as moving liquid or blood in a vessel, whereby a current JT cryoprobe doesn't have the capacity to form ice around the probe. Thereby, the current JT cryotechnology is generally ineffective to sufficiently propagate ice into tissue surrounding a blood vessel.
In addition, the high pressures required for argon-based JT cooling (e.g., 2000 PSI pressure drop) precluded its use within catheters, whereby their nonmetallic walls are generally rated only up to 500 PSI.
Since cooling of Argon gas occurs at the JT nozzle within an expansion chamber, producing a circumferential ablation of reasonable length (e.g., >1 cm) would be very difficult. The expansion chamber at the tip of the catheter would need to be similar to those used inside current metal cryoneedles or probes and would cause limited cooling.
A previous solution to the high pressure required in argon-based JT cooling is the use of nitrous-oxide cryogens. JT cooling can be done within a catheter using a cryogen which requires a much lower pressure drop, such as nitrous oxide. However, nitrous oxide generally only produces cooling at the tip of the cryoprobe/catheter surface of no lower than −60° C. In addition, cryoplasty research acknowledges that it is not possible to get much colder than −10° C. at the balloon surface, let alone into the surrounding artery wall.
Another cryoablation system uses a fluid at a near critical or supercritical state. Such cryoablation systems are described in U.S. Pat. Nos. 7,083,612 and 7,273,479. These systems have some advantages over previous systems. The benefits arise from the fluid having a gas-like viscosity. Having operating conditions near the critical point of nitrogen enables the system to avoid the undesirable phenomena of vapor lock associated with JT cooling while still providing good heat capacity. Additionally, such cryosystems can use very small channel probes and operate at pressures below 500 PSI for use in non-metal catheters.
However, challenges arise from use of a near-critical cryogen in a cryoablation system. In particular, there is still a significant density change in nitrogen (about 8 times) once it is crossing its critical point—resulting in the need for long pre-cooling times of the instrument. The heat capacity is high only close to the critical point and the system is very inefficient at higher temperatures requiring long pre-cooling times. Additionally, the system does not warm up (or thaw) the cryoprobe efficiently. Additionally, near-critical cryogen systems require a custom cryogenic pump(s) which is more difficult to create and service.
Still other types of thermo-based ablation systems are described in the patent literature. U.S. Pat. Nos. 5,957,963; 6,161,543; 6,241,722; 6,767,346; 6,936,045; 7,617,005 and International Patent Application No. PCT/US2008/084004, filed Nov. 19, 2008, describe various thermo-based ablation probes including malleable and flexible cryoprobes. Examples of patents describing cryoablation systems for supplying liquid nitrogen, nitrous oxide, argon, krypton, and other cryogens or different combinations thereof combined with Joule-Thomson effect include U.S. Pat. Nos. 5,520,682; 5,787,715; 5,956,958; 6074572; 6,530,234; and 6,981,382.
Notwithstanding the above, a cryotechnology system is desirable that has: 1.) sufficient cooling to cause renal neuromodulation, 2.) an operating size and shape to be used with an endovascular catheter of preferably less than 3 mm diameter (i.e., 9 French) and 3.) the ability to cause circumferential and/or partial circumferential intense cooling of the artery wall.
Various cryo-energy delivering balloon catheters have been described in the patent literature. U.S. Pat. No. 6,736,809, for example, is directed to a method for treating an aneurysm by cooling a target tissue region of the aneurysm to a temperature below a target temperature for a preselected time period. The method entails thickening, strengthening, or increasing the density of a blood vessel wall by cooling the blood vessel wall with a cryogenically cooled device. In particular, a device having a heat conductive cooling chamber is disposed proximate to the aneurysm site; and a cryogenic fluid coolant is directed to flow inside the chamber to create endothermic cooling relative to the aneurysm.
U.S. Pat. No. 6,283,959 is also directed to a cryo-energy delivery device. The device described in the '959 patent uses carbon dioxide (CO2) and has a metallic balloon surface with different patterns for greater thermal conductivity. The '959 patent describes use of a non-toxic fluid to fill the balloon such as CO2, or nitrous oxide (N2O), in case of balloon rupture. The '959 patent also describes use of evaporative and JT cooling aspects by injecting a predominant liquid mixture under pressure and allowing evaporation and gas expansion. In addition, these gases are generally functional within the engineering constraints of most balloons and catheters of less than 500 psi pressure. However, with CO2 and N2O having respective boiling points of −78.5° C. and −88.5° C., the surface temperatures of a balloon in contact with a vessel wall inside the high heat load region of a blood vessel generally achieves only −10° C. as previously noted from cryoplasty experience. It is therefore uncertain, or perhaps unlikely, that any of the desired “positive remodeling” needed to keep an artery open to its balloon-dilated extent would be possible since temperatures required to get this stent-like effect need to be less than −40° C. See references 10,11 herein.
This has implications for the renal artery which can have stenoses that actually cause “renal” hypertension by means of what was originally thought to be solely a compensatory response of the renin-angiotensin hormone system releasing these hormones in response to apparent low blood pressure within the renal artery and/or a kidney distal to the stenosis, thus causing overall hypertension in the remainder of the body to just keep the pressure gradient within the kidney. This is as opposed to “essential” hypertension in patients with more normal appearing renal artery lumens. Of note, large trials assessing blood pressure responses to extensive use of angioplasty and stents for renal artery stenoses in patients with resistant hypertension within the last two decades found no significant improvement in overall hypertension levels. Therefore, while the renin-angiotensin system may play an initial compensatory role, there is still the need for a technology and method which treats long-term persistent hypertension after angioplasty and/or stenting.
Renal artery stenting in many patients with hypertension also raises the issue of
RF ablation being incompatible with the metal stents in most of these patients. A new technology is needed which can effectively cause renal sympathetic nervous system (RSNA) modulation while also contributing to some aspect of positive remodeling of the renal artery lumen in patients with stenosis, or especially in patients with indwelling prior metal stents.In addition, if nerve ablation is desired for treating hypertension by ablating the renal nerve within and/or surrounding the renal artery wall, temperatures of −60° C. or below may be needed for long-term prevention of renal nerve regrowth that may impact the long-term duration of lowered blood pressure after ablation. Therefore, it is uncertain, if not unlikely, that the above described cryo-balloons can achieve the desired temperatures within a biological system because of the physical limitations necessary for evaporative or JT-based cryosystems.
The above mentioned '809 and '959 patents do not describe a design for the generation of sufficiently low temperatures to obtain the desired cryo-physiologic response. Insufficient generation of cold temperatures arise from the physical limitations of the cooling mechanisms, as well as the physical engineering limitations, proposed in the above mentioned patents.
An improved cryoablation catheter and/or associated balloon configuration that achieves minimal temperatures of less than −40° C. within several millimeters of the balloon and/or endoluminal surface of the vessel wall, is desirable to achieve desired vascular effects from positive remodeling. This is desirable in treating, for example, aneurysms, and to treat hypertension by renal nerve ablation.
A cryoablation balloon catheter design is desirable that achieves the necessary therapeutic temperatures within the engineering and anatomical constraints.
A method that has a substantially greater cooling power than is currently attainable through JT cooling to overcome the heat sink of the flowing blood within the renal artery, and to penetrate a thickened, atherosclerotic renal artery wall is therefore desirable.